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Q99497 (PARK7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein DJ-1

EC=3.4.-.-
Alternative name(s):
Oncogene DJ1
Parkinson disease protein 7
Gene names
Name:PARK7
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length189 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Protects cells against oxidative stress and cell death. Plays a role in regulating expression or stability of the mitochondrial uncoupling proteins SLC25A14 and SLC25A27 in dopaminergic neurons of the substantia nigra pars compacta and attenuates the oxidative stress induced by calcium entry into the neurons via L-type channels during pacemaking. Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death. May act as an atypical peroxiredoxin-like peroxidase that scavenges hydrogen peroxide. Following removal of a C-terminal peptide, displays protease activity and enhanced cytoprotective action against oxidative stress-induced apoptosis. Stabilizes NFE2L2 by preventing its association with KEAP1 and its subsequent ubiquitination. Binds to OTUD7B and inhibits its deubiquitinating activity. Enhances RELA nuclear translocation. Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress. Required for correct mitochondrial morphology and function and for autophagy of dysfunctional mitochondria. Regulates astrocyte inflammatory responses. Acts as a positive regulator of androgen receptor-dependent transcription. Prevents aggregation of SNCA. Plays a role in fertilization. Has no proteolytic activity. Has cell-growth promoting activity and transforming activity. May function as a redox-sensitive chaperone. May regulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells. Ref.1 Ref.11 Ref.14 Ref.18 Ref.19 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.33 Ref.35

Subunit structure

Homodimer. Binds EFCAB6/DJBP and PIAS2. Part of a ternary complex containing PARK7, EFCAB6/DJBP and AR. Interacts (via N-terminus) with OTUD7B. Interacts with BBS1, HIPK1, CLCF1 and MTERF. Ref.11 Ref.12 Ref.14 Ref.22 Ref.28 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34

Subcellular location

Cell membrane; Lipid-anchor. Cytoplasm. Nucleus. Membrane raft. Mitochondrion. Note: Under normal conditions, located predominantly in the cytoplasm and, to a lesser extent, in the nucleus and mitochondrion. Translocates to the mitochondrion and subsequently to the nucleus in response to oxidative stress and exerts an increased cytoprotective effect against oxidative damage. Detected in tau inclusions in brains from neurodegenerative disease patients. Membrane raft localization in astrocytes and neuronal cells requires palmitoylation. Ref.1 Ref.11 Ref.12 Ref.15 Ref.16 Ref.21 Ref.22 Ref.25 Ref.29 Ref.35 Ref.37

Tissue specificity

Highly expressed in pancreas, kidney, skeletal muscle, liver, testis and heart. Detected at slightly lower levels in placenta and brain. Detected in astrocytes, Sertoli cells, spermatogonia, spermatids and spermatozoa. Ref.1 Ref.15 Ref.16 Ref.17

Induction

By hydrogen peroxide and UV irradiation. Ref.18 Ref.21

Post-translational modification

Sumoylated on Lys-130 by PIAS2 or PIAS4; which is enhanced after ultraviolet irradiation and essential for cell-growth promoting activity and transforming activity. Ref.21

Cys-106 is easily oxidized to sulfinic acid.

Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress.

Involvement in disease

Parkinson disease 7 (PARK7) [MIM:606324]: A neurodegenerative disorder characterized by resting tremor, postural tremor, bradykinesia, muscular rigidity, anxiety and psychotic episodes. PARK7 has onset before 40 years, slow progression and initial good response to levodopa. Some patients may show traits reminiscent of amyotrophic lateral sclerosis-parkinsonism/dementia complex (Guam disease).
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Ref.13 Ref.36 Ref.37 Ref.39 Ref.40 Ref.41 Ref.44

Sequence similarities

Belongs to the peptidase C56 family.

Biophysicochemical properties

Kinetic parameters:

KM=173.4 µM for casein Ref.26

Ontologies

Keywords
   Biological processAutophagy
Fertilization
Inflammatory response
Stress response
   Cellular componentCell membrane
Cytoplasm
Membrane
Mitochondrion
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Neurodegeneration
Parkinson disease
Parkinsonism
Tumor suppressor
   LigandRNA-binding
   Molecular functionChaperone
Hydrolase
Protease
   PTMAcetylation
Isopeptide bond
Lipoprotein
Oxidation
Palmitate
Phosphoprotein
Ubl conjugation
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processadult locomotory behavior

Inferred from electronic annotation. Source: Ensembl

autophagy

Inferred from electronic annotation. Source: UniProtKB-KW

cell death

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to hydrogen peroxide

Inferred from direct assay Ref.18. Source: UniProtKB

dopamine uptake involved in synaptic transmission

Inferred from electronic annotation. Source: Ensembl

hydrogen peroxide metabolic process

Inferred from electronic annotation. Source: Ensembl

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

membrane depolarization

Inferred from electronic annotation. Source: Ensembl

membrane hyperpolarization

Inferred from electronic annotation. Source: Ensembl

mitochondrion organization

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of extrinsic apoptotic signaling pathway

Inferred from mutant phenotype PubMed 21785459. Source: UniProtKB

negative regulation of neuron apoptotic process

Inferred from direct assay PubMed 22511790. Source: BHF-UCL

negative regulation of protein binding

Inferred from direct assay Ref.11. Source: UniProtKB

positive regulation of oxidative phosphorylation uncoupler activity

Inferred from electronic annotation. Source: Ensembl

protein stabilization

Inferred from mutant phenotype Ref.23. Source: UniProtKB

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of androgen receptor signaling pathway

Inferred from direct assay Ref.11. Source: UniProtKB

regulation of inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

single fertilization

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Inferred from mutant phenotype PubMed 21785459. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 19199708PubMed 20458337. Source: UniProt

membrane raft

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from direct assay Ref.25. Source: UniProtKB

nucleus

Inferred from direct assay Ref.11Ref.25. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionmRNA binding

Inferred from direct assay Ref.24. Source: UniProtKB

peptidase activity

Inferred from direct assay Ref.26. Source: UniProtKB

peroxidase activity

Inferred from sequence or structural similarity. Source: UniProtKB

peroxiredoxin activity

Inferred from electronic annotation. Source: Ensembl

protein homodimerization activity

Inferred from direct assay Ref.25. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – ?Protein DJ-1PRO_0000157849
Propeptide? – 189Removed in mature formPRO_0000405558

Sites

Active site1061 Probable
Active site1261 Probable

Amino acid modifications

Modified residue671Phosphotyrosine Ref.20
Modified residue1061Cysteine sulfinic acid (-SO2H); alternate
Modified residue1481N6-acetyllysine By similarity
Modified residue1821N6-succinyllysine By similarity
Lipidation461S-palmitoyl cysteine Ref.29
Lipidation531S-palmitoyl cysteine Ref.29
Lipidation1061S-palmitoyl cysteine; alternate
Cross-link130Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.21

Natural variations

Natural variant261M → I in PARK7; does not affect protein stability and degradation; does not interfere with homodimerization. Ref.13 Ref.36
VAR_020492
Natural variant641E → D in PARK7; no apparent effect on protein stability; impaired mitochondrial morphology. Ref.39 Ref.40 Ref.45
VAR_020493
Natural variant981R → Q. Ref.36 Ref.38 Ref.41 Ref.42
Corresponds to variant rs71653619 [ dbSNP | Ensembl ].
VAR_020494
Natural variant1041A → T in PARK7. Ref.41
VAR_020495
Natural variant1491D → A in PARK7. Ref.36
Corresponds to variant rs74315352 [ dbSNP | Ensembl ].
VAR_020496
Natural variant1501G → S. Ref.10
VAR_020497
Natural variant1631E → K. Ref.43
VAR_034801
Natural variant1661L → P in PARK7; reduces protein stability and leads to increased degradation; interferes with homodimerization; abolishes interaction with PIAS2; strongly reduces chaperone activity; ubiquitinated by PARK2, leading to its recognition by HDAC6 and targeting to aggresome where is degraded. Ref.12 Ref.13 Ref.37 Ref.40 Ref.44
Corresponds to variant rs28938172 [ dbSNP | Ensembl ].
VAR_020498
Natural variant1711A → S. Ref.41
VAR_020499

Experimental info

Mutagenesis461C → A: Reduced localization in lipid rafts; when associated with A-106. Ref.19 Ref.25 Ref.29 Ref.35
Mutagenesis461C → A: Reduces protein stability. No effect on oxidation. Ref.19 Ref.25 Ref.29 Ref.35
Mutagenesis461C → S: No effect on mitochondrial translocation. Ref.19 Ref.25 Ref.29 Ref.35
Mutagenesis511V → A: Disrupts dimer formation and strongly reduces ability to eliminate hydrogen peroxide. Ref.18
Mutagenesis531C → A: Strongly reduces chaperone activity and ability to eliminate hydrogen peroxide. Ref.18 Ref.19 Ref.25 Ref.35
Mutagenesis531C → S: No effect on mitochondrial translocation. Ref.18 Ref.19 Ref.25 Ref.35
Mutagenesis1061C → A: Abolishes oxidation, association with mitochondria and protease activity. No effect on chaperone activity. Reduced binding to OTUD7B. Ref.19 Ref.22 Ref.25 Ref.26 Ref.28 Ref.29 Ref.35
Mutagenesis1061C → A: Reduced localization in lipid rafts; when associated with A-46. Ref.19 Ref.22 Ref.25 Ref.26 Ref.28 Ref.29 Ref.35
Mutagenesis1061C → D: Abolishes oxidation and association with mitochondria. No effect on chaperone activity. Ref.19 Ref.22 Ref.25 Ref.26 Ref.28 Ref.29 Ref.35
Mutagenesis1061C → S: No effect on mitochondrial translocation. Reduced protease activity. Ref.19 Ref.22 Ref.25 Ref.26 Ref.28 Ref.29 Ref.35
Mutagenesis1261H → A: Abolishes protease activity. Ref.26
Mutagenesis1301K → R: Partially compensates for loss of stability; when associated with P-166. Ref.12
Mutagenesis1661L → P: Reduced localization in lipid rafts. Ref.29
Sequence conflict1191F → C in BAB71782. Ref.3

Secondary structure

....................................... 189
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q99497 [UniParc].

Last modified July 5, 2004. Version 2.
Checksum: 4B21661B3A76BC67

FASTA18919,891
        10         20         30         40         50         60 
MASKRALVIL AKGAEEMETV IPVDVMRRAG IKVTVAGLAG KDPVQCSRDV VICPDASLED 

        70         80         90        100        110        120 
AKKEGPYDVV VLPGGNLGAQ NLSESAAVKE ILKEQENRKG LIAAICAGPT ALLAHEIGFG 

       130        140        150        160        170        180 
SKVTTHPLAK DKMMNGGHYT YSENRVEKDG LILTSRGPGT SFEFALAIVE ALNGKEVAAQ 


VKAPLVLKD 

« Hide

References

« Hide 'large scale' references
[1]"DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras."
Nagakubo D., Taita T., Kitaura H., Ikeda M., Tamai K., Iguchi-Ariga S.M.M., Ariga H.
Biochem. Biophys. Res. Commun. 231:509-513(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Cervix carcinoma.
[2]"Homo sapiens RNA-binding protein regulatory subunit mRNA."
Beaudoin R., Hod Y.
Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Lung.
[3]"Human DJ-1 cDNA from PC3 cells."
Ariga H., Niki T.
Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Thalamus.
[5]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Cervix.
[8]"Molecular cloning of human and mouse DJ-1 genes and identification of Sp1-dependent activation of the human DJ-1 promoter."
Taira T., Takahashi K., Kitagawa R., Iguchi-Ariga S.M.M., Ariga H.
Gene 263:285-292(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6.
Tissue: Kidney.
[9]Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 6-27; 33-89; 99-122 AND 149-175, MASS SPECTROMETRY.
Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[10]"DJ-1 gene G150S mutation."
Zou H.Q., Chan P.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 138-189, VARIANT SER-150.
[11]"DJ-1 positively regulates the androgen receptor by impairing the binding of PIASx alpha to the receptor."
Takahashi K., Taira T., Niki T., Seino C., Iguchi-Ariga S.M.M., Ariga H.
J. Biol. Chem. 276:37556-37563(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIAS2, SUBCELLULAR LOCATION, FUNCTION.
[12]"L166P mutant DJ-1, causative for recessive Parkinson's disease, is degraded through the ubiquitin-proteasome system."
Miller D.W., Ahmad R., Hague S., Baptista M.J., Canet-Aviles R., McLendon C., Carter D.M., Zhu P.-P., Stadler J., Chandran J., Klinefelter G.R., Blackstone C., Cookson M.R.
J. Biol. Chem. 278:36588-36595(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DEGRADATION BY THE PROTEASOME, SUBCELLULAR LOCATION, INTERACTION WITH PIAS2, HOMODIMERIZATION, MUTAGENESIS OF LYS-130, CHARACTERIZATION OF VARIANT PARK7 PRO-166.
[13]"A missense mutation (L166P) in DJ-1, linked to familial Parkinson's disease, confers reduced protein stability and impairs homo-oligomerization."
Moore D.J., Zhang L., Dawson T.M., Dawson V.L.
J. Neurochem. 87:1558-1567(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DEGRADATION BY THE PROTEASOME, CHARACTERIZATION OF VARIANTS PARK7 ILE-26 AND PRO-166.
[14]"DJBP: a novel DJ-1-binding protein, negatively regulates the androgen receptor by recruiting histone deacetylase complex, and DJ-1 antagonizes this inhibition by abrogation of this complex."
Niki T., Takahashi-Niki K., Taira T., Iguchi-Ariga S.M.M., Ariga H.
Mol. Cancer Res. 1:247-261(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EFCAB6, FUNCTION.
[15]"Immunocytochemical localization of DJ-1 in human male reproductive tissue."
Yoshida K., Sato Y., Yoshiike M., Nozawa S., Ariga H., Iwamoto T.
Mol. Reprod. Dev. 66:391-397(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[16]"DJ-1 colocalizes with tau inclusions: a link between parkinsonism and dementia."
Rizzu P., Hinkle D.A., Zhukareva V., Bonifati V., Severijnen L.-A., Martinez D., Ravid R., Kamphorst W., Eberwine J.H., Lee V.M.-Y., Trojanowski J.Q., Heutink P.
Ann. Neurol. 55:113-118(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[17]"The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease."
Bandopadhyay R., Kingsbury A.E., Cookson M.R., Reid A.R., Evans I.M., Hope A.D., Pittman A.M., Lashley T., Canet-Aviles R., Miller D.W., McLendon C., Strand C., Leonard A.J., Abou-Sleiman P.M., Healy D.G., Ariga H., Wood N.W., de Silva R. expand/collapse author list , Revesz T., Hardy J.A., Lees A.J.
Brain 127:420-430(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[18]"DJ-1 has a role in antioxidative stress to prevent cell death."
Taira T., Saito Y., Niki T., Iguchi-Ariga S.M., Takahashi K., Ariga H.
EMBO Rep. 5:213-218(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION, MUTAGENESIS OF VAL-51 AND CYS-53.
[19]"DJ-1 is a redox-dependent molecular chaperone that inhibits alpha-synuclein aggregate formation."
Shendelman S., Jonason A., Martinat C., Leete T., Abeliovich A.
PLoS Biol. 2:1-10(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF CYS-46; CYS-53 AND CYS-106.
[20]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-67, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]"Proper SUMO-1 conjugation is essential to DJ-1 to exert its full activities."
Shinbo Y., Niki T., Taira T., Ooe H., Takahashi-Niki K., Maita C., Seino C., Iguchi-Ariga S.M.M., Ariga H.
Cell Death Differ. 13:96-108(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-130, OXIDATION, SUBCELLULAR LOCATION, INDUCTION, FUNCTION.
[22]"DJ-1 interacts with HIPK1 and affects H2O2-induced cell death."
Sekito A., Koide-Yoshida S., Niki T., Taira T., Iguchi-Ariga S.M.M., Ariga H.
Free Radic. Res. 40:155-165(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HIPK1, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-106.
[23]"DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2."
Clements C.M., McNally R.S., Conti B.J., Mak T.W., Ting J.P.
Proc. Natl. Acad. Sci. U.S.A. 103:15091-15096(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[24]"RNA binding activity of the recessive parkinsonism protein DJ-1 supports involvement in multiple cellular pathways."
van der Brug M.P., Blackinton J., Chandran J., Hao L.Y., Lal A., Mazan-Mamczarz K., Martindale J., Xie C., Ahmad R., Thomas K.J., Beilina A., Gibbs J.R., Ding J., Myers A.J., Zhan M., Cai H., Bonini N.M., Gorospe M., Cookson M.R.
Proc. Natl. Acad. Sci. U.S.A. 105:10244-10249(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[25]"Mitochondrial localization of DJ-1 leads to enhanced neuroprotection."
Junn E., Jang W.H., Zhao X., Jeong B.S., Mouradian M.M.
J. Neurosci. Res. 87:123-129(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-46; CYS-53 AND CYS-106.
[26]"Parkinson disease protein DJ-1 converts from a zymogen to a protease by carboxyl-terminal cleavage."
Chen J., Li L., Chin L.S.
Hum. Mol. Genet. 19:2395-2408(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVE SITES, MUTAGENESIS OF CYS-106 AND HIS-126.
[27]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"DJ-1 enhances cell survival through the binding of cezanne, a negative regulator of NF-{kappa}B."
McNally R.S., Davis B.K., Clements C.M., Accavitti-Loper M.A., Mak T.W., Ting J.P.
J. Biol. Chem. 286:4098-4106(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH BBS1; CLCF1; MTERF AND OTUD7B, MUTAGENESIS OF CYS-106.
[29]"DJ-1 associates with lipid rafts by palmitoylation and regulates lipid rafts-dependent endocytosis in astrocytes."
Kim K.S., Kim J.S., Park J.Y., Suh Y.H., Jou I., Joe E.H., Park S.M.
Hum. Mol. Genet. 22:4805-4817(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PALMITOYLATION AT CYS-46; CYS-53 AND CYS-106, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-46; CYS-106 AND LEU-166.
[30]"Crystal structure of DJ-1/RS and implication on familial Parkinson's disease."
Huai Q., Sun Y., Wang H., Chin L.-S., Li L., Robinson H., Ke H.
FEBS Lett. 549:171-175(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS), HOMODIMERIZATION.
[31]"Crystal structure of human DJ-1, a protein associated with early onset Parkinson's disease."
Tao X., Tong L.
J. Biol. Chem. 278:31372-31379(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF WILD-TYPE AND MUTANT ARG-130, HOMODIMERIZATION.
[32]"The crystal structure of DJ-1, a protein related to male fertility and Parkinson's disease."
Honbou K., Suzuki N.N., Horiuchi M., Niki T., Taira T., Ariga H., Inagaki F.
J. Biol. Chem. 278:31380-31384(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS), HOMODIMERIZATION.
[33]"Crystal structures of human DJ-1 and Escherichia coli Hsp31, which share an evolutionarily conserved domain."
Lee S.-J., Kim S.J., Kim I.-K., Ko J., Jeong C.-S., Kim G.-H., Park C., Kang S.-O., Suh P.-G., Lee H.-S., Cha S.-S.
J. Biol. Chem. 278:44552-44559(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), FUNCTION, OXIDATION, HOMODIMERIZATION.
[34]"The 1.1-A resolution crystal structure of DJ-1, the protein mutated in autosomal recessive early onset Parkinson's disease."
Wilson M.A., Collins J.L., Hod Y., Ringe D., Petsko G.A.
Proc. Natl. Acad. Sci. U.S.A. 100:9256-9261(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.1 ANGSTROMS), HOMODIMERIZATION, OXIDATION, LACK OF PROTEOLYTIC ACTIVITY.
[35]"The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization."
Canet-Aviles R.M., Wilson M.A., Miller D.W., Ahmad R., McLendon C., Bandyopadhyay S., Baptista M.J., Ringe D., Petsko G.A., Cookson M.R.
Proc. Natl. Acad. Sci. U.S.A. 101:9103-9108(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS), MUTAGENESIS OF CYS-46; CYS-53 AND CYS-106, OXIDATION, FUNCTION, SUBCELLULAR LOCATION.
[36]"The role of pathogenic DJ-1 mutations in Parkinson's disease."
Abou-Sleiman P.M., Healy D.G., Quinn N., Lees A.J., Wood N.W.
Ann. Neurol. 54:283-286(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PARK7 ILE-26 AND ALA-149, VARIANT GLN-98.
[37]"Mutations in the DJ-1 gene associated with autosomal recessive early-onset Parkinsonism."
Bonifati V., Rizzu P., van Baren M.J., Schaap O., Breedveld G.J., Krieger E., Dekker M.C.J., Squitieri F., Ibanez P., Joosse M., van Dongen J.W., Vanacore N., van Swieten J.C., Brice A., Meco G., van Duijn C.M., Oostra B.A., Heutink P.
Science 299:256-259(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK7 PRO-166, SUBCELLULAR LOCATION.
[38]"The R98Q variation in DJ-1 represents a rare polymorphism."
Hedrich K., Schaefer N., Hering R., Hagenah J., Lanthaler A.J., Schwinger E., Kramer P.L., Ozelius L.J., Bressman S.B., Abbruzzese G., Martinelli P., Kostic V., Pramstaller P.P., Vieregge P., Riess O., Klein C.
Ann. Neurol. 55:145-146(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLN-98.
[39]"Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7)."
Hering R., Strauss K.M., Tao X., Bauer A., Woitalla D., Mietz E.M., Petrovic S., Bauer P., Schaible W., Mueller T., Schoels L., Klein C., Berg D., Meyer P.T., Schulz J.B., Wollnik B., Tong L., Krueger R., Riess O.
Hum. Mutat. 24:321-329(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK7 ASP-64, X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[40]"Differential effects of Parkinson's disease-associated mutations on stability and folding of DJ-1."
Goerner K., Holtorf E., Odoy S., Nuscher B., Yamamoto A., Regula J.T., Beyer K., Haass C., Kahle P.J.
J. Biol. Chem. 279:6943-6951(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS PARK7 ASP-64 AND PRO-166.
[41]"Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations."
Clark L.N., Afridi S., Mejia-Santana H., Harris J., Louis E.D., Cote L.J., Andrews H., Singleton A., Wavrant De-Vrieze F., Hardy J., Mayeux R., Fahn S., Waters C., Ford B., Frucht S., Ottman R., Marder K.
Mov. Disord. 19:796-800(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PARK7 THR-104, VARIANTS GLN-98 AND SER-171.
[42]"DJ-1 (PARK7) mutations are less frequent than Parkin (PARK2) mutations in early-onset Parkinson disease."
Hedrich K., Djarmati A., Schafer N., Hering R., Wellenbrock C., Weiss P.H., Hilker R., Vieregge P., Ozelius L.J., Heutink P., Bonifati V., Schwinger E., Lang A.E., Noth J., Bressman S.B., Pramstaller P.P., Riess O., Klein C.
Neurology 62:389-394(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLN-98.
[43]"DJ-1 mutations and parkinsonism-dementia-amyotrophic lateral sclerosis complex."
Annesi G., Savettieri G., Pugliese P., D'Amelio M., Tarantino P., Ragonese P., La Bella V., Piccoli T., Civitelli D., Annesi F., Fierro B., Piccoli F., Arabia G., Caracciolo M., Ciro Candiano I.C., Quattrone A.
Ann. Neurol. 58:803-807(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LYS-163.
[44]"Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6."
Olzmann J.A., Li L., Chudaev M.V., Chen J., Perez F.A., Palmiter R.D., Chin L.S.
J. Cell Biol. 178:1025-1038(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT PARK7 PRO-166.
[45]"Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson's disease-associated protein DJ-1."
Krebiehl G., Ruckerbauer S., Burbulla L.F., Kieper N., Maurer B., Waak J., Wolburg H., Gizatullina Z., Gellerich F.N., Woitalla D., Riess O., Kahle P.J., Proikas-Cezanne T., Kruger R.
PLoS ONE 5:E9367-E9367(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASP-64.
+Additional computationally mapped references.

Web resources

GeneReviews
SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D61380 mRNA. Translation: BAA09603.2.
AF021819 mRNA. Translation: AAC12806.1.
AB073864 mRNA. Translation: BAB71782.1.
AK312000 mRNA. Translation: BAG34938.1.
AL034417 Genomic DNA. Translation: CAB52550.1.
CH471130 Genomic DNA. Translation: EAW71591.1.
BC008188 mRNA. Translation: AAH08188.1.
AB045294 Genomic DNA. No translation available.
AY648999 Genomic DNA. Translation: AAT68961.1.
PIRJC5394.
RefSeqNP_001116849.1. NM_001123377.1.
NP_009193.2. NM_007262.4.
XP_005263481.1. XM_005263424.1.
UniGeneHs.419640.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1J42X-ray2.50A1-189[»]
1P5FX-ray1.10A1-189[»]
1PDVX-ray1.80A1-189[»]
1PDWX-ray2.20A/B/C/D/E/F/G/H1-189[»]
1PE0X-ray1.70A/B1-189[»]
1Q2UX-ray1.60A1-189[»]
1SOAX-ray1.20A1-189[»]
1UCFX-ray1.95A/B1-189[»]
2OR3X-ray1.20A/B1-189[»]
2R1TX-ray1.70A/B2-188[»]
2R1UX-ray1.50A/B2-188[»]
2R1VX-ray1.70A/B2-188[»]
2RK3X-ray1.05A1-189[»]
2RK4X-ray1.15A1-189[»]
2RK6X-ray1.15A1-189[»]
3B36X-ray1.50A1-189[»]
3B38X-ray1.85A1-189[»]
3B3AX-ray1.50A1-189[»]
3BWEX-ray2.40A/B/C/D/E/F/G1-189[»]
3CY6X-ray1.35A1-189[»]
3CYFX-ray1.60A1-189[»]
3CZ9X-ray1.15A1-189[»]
3CZAX-ray1.20A1-189[»]
3EZGX-ray1.15A1-189[»]
3F71X-ray1.20A1-189[»]
3SF8X-ray1.56A/B1-189[»]
4BTEX-ray1.38A1-189[»]
ProteinModelPortalQ99497.
SMRQ99497. Positions 3-188.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116446. 62 interactions.
DIPDIP-35515N.
IntActQ99497. 31 interactions.
MINTMINT-5003468.
STRING9606.ENSP00000340278.

Protein family/group databases

MEROPSC56.002.

PTM databases

PhosphoSiteQ99497.

Polymorphism databases

DMDM56404943.

2D gel databases

OGPQ99497.
REPRODUCTION-2DPAGEIPI00298547.
UCD-2DPAGEO14805.
Q99497.

Proteomic databases

PaxDbQ99497.
PeptideAtlasQ99497.
PRIDEQ99497.

Protocols and materials databases

DNASU11315.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000338639; ENSP00000340278; ENSG00000116288.
ENST00000377488; ENSP00000366708; ENSG00000116288.
ENST00000377491; ENSP00000366711; ENSG00000116288.
ENST00000493373; ENSP00000465404; ENSG00000116288.
ENST00000493678; ENSP00000418770; ENSG00000116288.
GeneID11315.
KEGGhsa:11315.
UCSCuc001aou.4. human.

Organism-specific databases

CTD11315.
GeneCardsGC01P008014.
HGNCHGNC:16369. PARK7.
HPACAB005870.
HPA004190.
MIM168600. phenotype.
602533. gene.
606324. phenotype.
neXtProtNX_Q99497.
Orphanet90020. Amyotrophic lateral sclerosis-parkinsonism-dementia complex.
2828. Young adult-onset Parkinsonism.
PharmGKBPA32946.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0693.
HOGENOMHOG000063194.
HOVERGENHBG053511.
InParanoidQ99497.
KOK05687.
OMAATCYPGF.
OrthoDBEOG7CVPZX.
PhylomeDBQ99497.
TreeFamTF300119.

Enzyme and pathway databases

SignaLinkQ99497.

Gene expression databases

ArrayExpressQ99497.
BgeeQ99497.
CleanExHS_PARK7.
GenevestigatorQ99497.

Family and domain databases

InterProIPR006287. DJ1.
IPR002818. ThiJ/PfpI.
[Graphical view]
PfamPF01965. DJ-1_PfpI. 1 hit.
[Graphical view]
TIGRFAMsTIGR01383. not_thiJ. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ99497.
GeneWikiPARK7.
GenomeRNAi11315.
NextBio42983.
PMAP-CutDBQ99497.
PROQ99497.
SOURCESearch...

Entry information

Entry namePARK7_HUMAN
AccessionPrimary (citable) accession number: Q99497
Secondary accession number(s): B2R4Z1 expand/collapse secondary AC list , O14805, Q6DR95, Q7LFU2
Entry history
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: July 5, 2004
Last modified: March 19, 2014
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM